These projects are designed to give information related to the 1) intracellular mechanisms responsible for the rapid decline of cardiac contractility during ischemia and 2) factors determining the behavior of these mechanisms such as ontogenetic differentiation of striated muscle types and patterns of use. The effects of changes in intracellular ionic conditions and energy stores ((H ion), (MgATP 2 minus), (CP 2 minus) known to be associated with ischemic negative inotropism will be determined on Ca 2 ion-activated contractile protein force generation, Ca 2 ion-cycling by the sarcoplasmic reticulum, and rate of Ca 2 ion-activated force generation of skinned (sarcolemma disrupted or removed) muscle fibers. Comparative studies of skeletal and cardiac fibers will be done because of the known differential effect of ischemia on striated muscle types. Since the resistance of adult soleus muscle to effects of acidosis and ischemia appears to be acquired during development, the effects of acidosis and MgATP 2 minus depletion on skinned fiber CA 2 ion-activated force generation will be determined for cardiac, adductor magnus, and soleus fibers of 26-day embryo, 5 day newborn, and adult rabbits. Pieces of the same fibers will be characterized histochemically (myofibrillar ATPase, succinic dehydrogenase, phosphorylase). Using contralateral skeletal muscles, normal and ischemic twitch tetanic force characteristics will be measured for each developmental phase. To assay plasticity of muscle, identical measurements will be made on chronically stimulated fast twitch rabbit skeletal muscle and the effects of acidosis and MgATP 2 minus depletion on cardiac skinned fiber force will be determined using left-ventricular tissue and papillary muscles from pressure hypertrophied and endurance trained (swimming) rats. Knowledge of alteration of cardiac sensitivity to acidosis and/or ischemia may be useful therapeutically.